ANG-II IS A MITOGEN FOR A MURINE CELL-LINE ISOLATED FROM MEDULLARY THICK ASCENDING LIMB OF HENLE-LOOP

A murine SV40-transformed renal epithelial cell line derived from medu llary thick ascending limb of Henle's loop (MTAL) was established and characterized by morphology, antigen expression, and biochemical crite ria. These MTAL cells express a single class of high-affinity receptor s for angiotensin II (ANG II) and transcripts for the AT(1) subtype of ANG II receptors. ANG II, in a dose-dependent manner, induced prolife ration of MTAL cells. This observation is in striking contrast to syng eneic proximal tubular cells in which it was previously shown that the peptide induced cellular hypertrophy and slightly inhibited prolifera tion IG. Wolf and E. G. Neilson. Am. J. Physiol. 259 (Renal Fluid Elec trolyte Physiol. 28: F768-F777, 1990]. The AT(1)-receptor antagonist l osartan (10(-6) M), but not an AT(2)-receptor antagonist, blocked the mitogenic effects of ANG II in MTAL cells. Coincubation of quiescent M TAL cells with ANG II and 5% fetal calf serum further increased prolif eration compared with cells grown only in serum. In contrast to proxim al tubular cells, ANG II failed to induce transforming growth factor-b eta 1 mRNA and protein synthesis in MTAL cells. Our data collectively suggest that ANG II is a mitogen for MTAL cells in vitro. Therefore, e pithelial cells derived from different parts of the nephron, even when transformed with SV40 virus and while under cell culture conditions, exhibit a distinct pattern of growth behavior after stimulation with A NG II.